A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab
Study Details
Study Description
Brief Summary
This is a phase 1/2, open-label, multi-center, first-in-human, two-stage (Part 1: dose escalation and Part 2: dose expansion) study evaluating multiple doses and schedules of intravenously (IV) administered HMBD-002, with or without pembrolizumab, in patients with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a phase 1/2, open-label, multi-center study whose principal phase 1 stage objective is to determine the recommended phase 2 dose (RP2D) of the anti-VISTA monoclonal antibody (mAb) as a single agent and combined with the anti-PD-1 mAb pembrolizumab in subjects with advanced solid malignancies.
In the phase 2 stage, the antitumor activity of HMBD-002 alone or combined with pembrolizumab will be evaluated in patients with triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC) and a wide range of other malignancies known or documented to express VISTA.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 - Dose Escalation Phase (Monotherapy) HMBD-002 administered as a 60-minute IV infusion as a monotherapy. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle. |
Drug: HMBD-002
IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
|
| Experimental: Part 1 - Dose Escalation Phase (Combination Therapy) HMBD-002 administered as a 60-minute IV infusion at escalating doses in combination with pembrolizumab. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle. Pembrolizumab will be administered as a 30-minute IV infusion at a dose of 200 mg on Day 1 of every 21-day cycle. |
Drug: HMBD-002
IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
Drug: Pembrolizumab
IgG4 mAb with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and programmed cell death ligand 2 (PD-L2).
|
| Experimental: Part 2 - Dose Expansion (Monotherapy) HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion as a monotherapy in patients with TNBC or NSCLC. |
Drug: HMBD-002
IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
|
| Experimental: Part 2 - Dose Expansion (Combination Therapy) HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion in combination with pembrolizumab at the standard labeled dose in patients with TNBC or NSCLC. |
Drug: HMBD-002
IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
Drug: Pembrolizumab
IgG4 mAb with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and programmed cell death ligand 2 (PD-L2).
|
Outcome Measures
Primary Outcome Measures
- Dose-limiting Toxicity [First 21 days of treatment.]
The incidence of DLTs during the DLT assessment period.
- Dose-Finding [Screening to 90 days from last dose.]
Determination of the MTD or maximum tested dose, and the RP2D.
- Frequency and Severity of Adverse Events (AE) [Screening to 90 days from last dose.]
The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.
Secondary Outcome Measures
- Pharmacokinetics of HMBD-002 [Day 1 of dosing through 21 days post last dose.]
Maximum Plasma Concentration (Cmax)
- Pharmacokinetics of HMBD-002 [Day 1 of dosing through 21 days post last dose.]
Area Under the Curve (AUC)
- Objective Response Rate (ORR) [Day 1 of dosing through every 90 after the last dose.]
ORR according to RECIST v1.1.
- Duration of Response (DoR) [Day 1 of dosing through every 90 after the last dose.]
Time from the date measurement criteria are first met for PR or CR to the date measurement criteria are first met for PD.
- Progression Free Survival (PFS) [Day 1 of dosing through every 90 after the last dose.]
Time from the date of initiation of study therapy to the date measurement criteria are first met for PD or death from any cause, whichever occurs first.
- Overall Survival (OS) [Day 1 of dosing through every 90 after the last dose.]
Time from the date of initiation of study therapy to the date of death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria (Phase 1 and 2 Stages)
-
Histologic or cytologic evidence of a malignant solid cancer (any histology) with advanced or metastatic disease and no available therapies known to confer clinical benefit.
-
Tumor tissue, or paraffin block, ideally from the patient's most recent biopsy. A fresh tumor biopsy will be obtained if archival samples are not available.
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Measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
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At least 18 years old.
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An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
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Adequate hematopoietic, kidney, and liver functions.
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A left ventricular ejection fraction (LVEF) ≥ 45%.
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Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding. A WOCBP must agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
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Male subjects must agree to follow contraceptive guidance during the study period and for at least 120 days after the last dose of study treatment.
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Patient must give informed written consent for the study.
Inclusion Criteria for HMBD-002 Phase 2 Stage
Triple Negative Breast Cancer (TNBC)
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Histologic or cytologic evidence of TNBC that is advanced or metastatic.
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Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
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Must have received appropriate treatment with at least one prior regimen for TNBC and there are no available therapies known to confer clinical benefit.
Non-Small Cell Lung Cancer (Monotherapy and Combination)
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Histologic or cytologic evidence of NSCLC that is advanced or metastatic.
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Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
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Absence of an activating mutation of the EGFR or ALK.
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Must have received treatment with an approved therapy if there are other genomic aberrations for which targeted therapies are approved and available.
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Must have had disease progression on at least one approved or comparable standard therapy for NSCLC.
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Must have received appropriate prior treatment with a mAb to PD-1 or PD-L1.
Multiple Other Cancers (Combination Therapy Baskets)
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Histologic or cytologic evidence of an advanced or metastatic cancer aside from TNBC and NSCLC with no available therapies known to confer clinical benefit.
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Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
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Must have had appropriate treatment for their specific cancer and there is an absence of available therapy with a reasonable likelihood of conferring clinical benefit.
Exclusion Criteria
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If the patient received prior therapy with an anti-PD-1 or anti-PD-L1 mAb or with an agent targeting stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event.
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Received radiotherapy within 2 weeks of treatment.
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Received radiotherapy exceeding 30 Gray (Gy) to the lung within 6 months of the first dose of study medication.
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Received an allogeneic tissue/solid organ transplant.
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Received a live or live-attenuated vaccine within 30 days prior to the first dose of study medication.
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Received a VISTA targeting agent.
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The patient must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
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The patient has an active autoimmune disease that required systemic treatment in the past.
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Presence of an uncontrolled endocrine disorder.
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Presence of clinically significant cardiovascular disease.
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History of (non-infectious) pneumonitis or interstitial pulmonary disease that required steroids or has current pneumonitis or interstitial pulmonary disease.
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Presence of uncontrolled, clinically significant pulmonary disease.
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A previous a severe hypersensitivity reaction (≥ Grade 3) to pembrolizumab and/or any of its excipients.
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A diagnosis of immunodeficiency or is receiving chronic systemic corticosteroids at a dose that exceeds 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
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An uncontrolled intercurrent illness that would limit compliance with the study.
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A positive status for human immunodeficiency virus (HIV).
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A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C viral (defined as HCV RNA detected) infection.
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Oxygen-dependence.
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A medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicity.
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A positive COVID test within one week of study treatment if not fully vaccinated.
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Another active malignancy that is progressing or has required active treatment within the past 3 years.
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Known active central nervous system metastases and/or carcinomatous meningitis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 2 | Stanford Cancer Institute | Palo Alto | California | United States | 94304 |
| 3 | Smilow Cancer Hospital - Yale New Heaven Health | New Haven | Connecticut | United States | 06511 |
| 4 | UTSW Medical Center | Dallas | Texas | United States | 75390 |
| 5 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 6 | Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77054 |
Sponsors and Collaborators
- Hummingbird Bioscience, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HMBD-002-V4C26-01